Low-dose alemtuzumab induction in a tailored immunosuppression protocol for sensitized kidney transplant recipients

Martina Guthoff,Silvio Nadalin,Nils Heyne,Tamam Bakchoul,Kilian Berger,Karina Althaus,Alfred Königsrainer,Wolfgang Steurer,Thomas Mühlbacher

doi:10.1186/s12882-020-01767-z

Abstract

BackgroundInduction therapy is crucial in kidney transplantation and constitutes an important cornerstone for long-term allograft survival. Alemtuzumab is a depleting CD52-specific antibody with T- and B-cell activity, leading to prolonged lymphocyte depletion for up to 12 months, with profound immunosuppression and an associated risk of serious infections. Current concepts aim to optimize dosing strategies to reduce side effects. Here we present data from an ongoing centre protocol consisting of low-dose alemtuzumab induction and tailored immunosuppression in sensitized patients undergoing kidney transplantation.Methods10-year results of the protocol were analysed. Low-dose alemtuzumab induction consisted of a single dose of 20 mg intraoperatively, followed by tacrolimus and corticosteroids for initial immunosuppression, with mycophenolate mofetil suspended until a total lymphocyte count (TLC) >5% or 200/μl was reached.ResultsBetween 01/2007 and 04/2017, 46 patients were treated in accordance with the protocol in 48 kidney transplantations. Median PRAmax was 43 [22-76; IQR] %; all patients had negative CDC-crossmatch prior to transplantation. Low-dose alemtuzumab was well tolerated. Median time to TLC recovery was 77 [62-127; IQR] d. Within a median follow-up of 3.3 [1.5-5.6; IQR] years, 12 (25%) patients developed BPAR, 10 of which were antibody-mediated (3 acute, 7 chronic ABMR). Death-censored 5-year allograft survival was 79.2%, with an excellent allograft function at the end of follow-up. There was no increased rate of infections, in particular viral infections.ConclusionsOur protocol, comprising low-dose alemtuzumab induction, initial suspension of mycophenolate mofetil and triple maintenance immunosuppression, provides excellent patient and allograft outcome in sensitized renal allograft recipients.

Highlights

Induction therapy is crucial in kidney transplantation and constitutes an important cornerstone for long-term allograft survival
Two different classes of agents are used for induction therapy: non-depleting antibodies, such as CD25 inhibitory antibodies (directed against the α-chain of interleukin 2 (IL2) receptor), which block Interleukin 2 (IL2)-mediated T-cell stimulation, and depleting antibodies, which lead to total lymphocyte depletion and include antithymocyte globulin (ATG) and the CD52 antibody alemtuzumab
Design and setting of the study All renal transplant recipients treated according to the centre induction protocol in kidney or simultaneous pancreas-kidney transplantation between 01/2007 and 04/2017 at the Tübingen University Hospital Collaborative Transplant Centre were included in the analysis

Summary

Introduction

Induction therapy is crucial in kidney transplantation and constitutes an important cornerstone for long-term allograft survival. Alemtuzumab is a depleting CD52-specific antibody with T- and B-cell activity, leading to prolonged lymphocyte depletion for up to 12 months, with profound immunosuppression and an associated risk of serious infections. We present data from an ongoing centre protocol consisting of low-dose alemtuzumab induction and tailored immunosuppression in sensitized patients undergoing kidney transplantation. Sensitized patients with pre-existing HLA-antibodies are at high risk of acute and chronic antibody-mediated rejection [4] and constitute a major challenge in kidney transplantation. Two different classes of agents are used for induction therapy: non-depleting antibodies, such as CD25 inhibitory antibodies (directed against the α-chain of interleukin 2 (IL2) receptor), which block IL2-mediated T-cell stimulation, and depleting antibodies, which lead to total lymphocyte depletion and include antithymocyte globulin (ATG) and the CD52 antibody alemtuzumab. Depleting antibodies have higher immunosuppressive potential than CD25 inhibitory antibodies [6,7,8]; associated concerns include over-immunosuppression with the risk of infection and other related side effects

Methods

Results

Conclusion